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Background: Obesity at diagnosis of childhood acute lymphoblastic leukemia (ALL) is associated with greater risk of relapse; whether this association extends to obesity during maintenance is unstudied., Methods: This study used data from AALL03N1 to calculate median body mass index (BMI) for 676 children over 6 consecutive months during maintenance therapy; BMI percentile (BMI%ile) were operationalized as normal/underweight (<85%ile), overweight/obese (85%-98%ile), and extreme obesity (≥99%ile). Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression after adjusting for all relevant demographic and clinical predictors., Results: Median age at study enrollment was 6 years and median length of follow-up was 7.9 years. Overall, 43.3% of the cohort was underweight/normal weight, 44.8% was overweight/obese, and 11.8% had extreme obesity. Cumulative incidence of relapse at 4 years from study enrollment was higher among those with extreme obesity (13.6% ± 4.5%) compared to those with underweight/normal weight (9.0% ± 2.1%). Multivariable analysis revealed that children with extreme obesity had a 2.4-fold (95% confidence interval [CI], 1.1-5.0; p = .01) greater hazard of relapse compared to those who were underweight/normal weight. Overweight/obese patients were at comparable risk to those who were underweight/normal weight (hazard ratio, 0.8; 95% CI, 0.4-1.6). Erythrocyte thioguanine nucleotide (TGN) levels were significantly lower among children with extreme obesity compared to those with underweight/normal weight (141.6 vs. 168.8 pmol/8 × 10 8 erythrocytes; p = .0002), however, the difference in TGN levels did not explain the greater hazard of relapse among those with extreme obesity., Conclusions: Extreme obesity during maintenance therapy is associated with greater hazard of relapse in children with ALL. Underlying mechanisms of this association needs further investigation., Lay Summary: Findings from this study demonstrate that extreme obesity during maintenance therapy is associated with a greater hazard of relapse among children with acute lymphoblastic leukemia. We show that children with obesity have lower levels of erythrocyte thioguanine nucleotides even after adjusting for adherence to oral chemotherapy. However, these lower levels do not explain the greater hazard of relapse, paving the way for future studies to explore this association., (© 2022 American Cancer Society.)

Background: Since 1975, there has been a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not had a similar improvement. Data indicate a direct correlation between increased cure rates and clinical trial enrollment., Methods: The authors previously published data indicating inferior clinical trial enrollment when AYA patients were treated at an adult oncology center versus a pediatric oncology center. To address this deficit, a joint pediatric and adult AYA Oncology Program was established in July 2006 with the primary objective of improving outcomes by increasing therapeutic clinical trial enrollment in this population. Patients who were referred to that program from July 2006 through June 2010 were examined retrospectively to establish whether clinical trial enrollment increased compared with historic controls., Results: Fifty-seven patients were referred to the program from 2006 to 2010 (range, 12-16 new patients per year). Eight patients were referred for consultation only and were not treated at the University of Pittsburgh Cancer Institute or Children's Hospital of Pittsburgh. Five of 22 patients (23%) who received treatment at the pediatric cancer center were enrolled onto a clinical trial, whereas 9 of 27 patients (33%) patients who received treatment at the adult cancer center were enrolled. There was superior trial participation compared with the previous 3 years for those shared AYA patients who were treated at the adult center (P < .001)., Conclusions: Data from this study demonstrated that establishing a unified AYA oncology program can lead to improved clinical trial enrollment for patients who are treated at medical oncology centers., (Copyright © 2011 American Cancer Society.)

Little is known about cisplatin ototoxicity in pediatric patients. Measurement of otoacoustic emissions is a rapid, reproducible, objective method of evaluating hearing. We examined whether transient-evoked otoacoustic emissions in pediatric patients exposed to cisplatin in the past correlated with audiographic findings. Twelve patients were entered into the study (mean age at treatment 7.8 years, mean cumulative dose 442.5 mg/mm2, mean 7.1 doses). Hearing at 3000 Hz was preserved in 82.6% of patients. In the higher frequencies significant sensorineural hearing loss was noted: 43.5% at 4 kHz; 81.0% at 6 kHz; and 90.5% at 8 kHz. Transient-evoked otoacoustic emissions were measurable in 11 of 12 patients. Middle ear disease accounted for abnormal otoacoustic emission seen in three patients (1 with effusion, 2 with significant negative middle ear pressure). When the middle ear was normal, a statistically significant correlation was seen between the transient-evoked otoacoustic emissions reproducibility and pure-tone threshold (correlation coefficient = -0.69, p = 0.008). Increased hearing loss was also associated with young age at first dose of cisplatin (p = 0.044), high number of chemotherapy cycles (p = 0.042), and high cumulative dose (p = 0.042).

The requirement of erythropoiesis for erythropoietin were studied in a patient with Ph chronic myelocytic leukemia who had undergone an erythroblastic transformation. Transfusions resulted in a suppression of erythropoiesis. Plasma clot culture studies indicated that both the CFU-E and BFU-E in the peripheral blood of this patient were dependent upon erythropoietin for their differentiation and proliferation. Neither of these committed erythroid stem cells was cloned in the absence of erythropoietin. These studies suggest that the proliferation and differentiation of erythroid stem cells during the erythroblastic crisis of this disorder remain dependent upon physiologic regulators.